SOS1 是 KRAS 的重要鸟嘌呤核苷酸交换因子。它促进 KRAS 从不活跃的 GDP 结合状态转变为活跃的 GTP 结合状态。 KRAS 的激活触发下游信号通路，促进肿瘤的发生和进展。抑制 SOS1 以防止 KRAS 激活是治疗 KRAS 驱动的肿瘤的有效策略。本次审查使用 Cortellis Drug Discovery Intelligence 识别了 2022 年 1 月至 2024 年 6 月期间发表的声称是 SOS1 抑制剂或 SOS1-KRAS 相互作用调节剂的专利。总共评估了来自 5 个不同申请人的 15 项专利申请。在 KRAS 驱动的肿瘤中，抑制 SOS1 通过调节 RAS/MAPK 和 PI3K/AKT/mTOR 信号通路显着影响细胞增殖和迁移。自 2022 年以来，已发布了大量 SOS1 抑制剂专利。大多数 SOS1 抑制剂目前处于临床前开发阶段，只有少数进展到临床试验。然而，这些抑制剂在临床研究中面临重大挑战，包括单一疗法的疗效有限、安全性问题以及增强 PK 特性的必要性。尽管 SOS1 抑制剂具有出色的体外性能，但在临床应用中必须解决与安全性、药代动力学和药效学相关的问题。

SOS1 is a crucial guanine nucleotide exchange factor for KRAS. It facilitates the transition of KRAS from inactive GDP-bound state to active GTP-bound state. The activation of KRAS triggers downstream signaling pathways, promoting tumor initiation and progression. Inhibiting SOS1 to prevent KRAS activation is an effective strategy for treating tumors driven by KRAS.This review identified patents claiming to be SOS1 inhibitors or SOS1-KRAS interaction modulators published between January 2022 and June 2024 using Cortellis Drug Discovery Intelligence. A total of 15 patent applications from 5 different applicants were assessed.In KRAS-driven tumors, inhibiting SOS1 significantly affect cell proliferation and migration by modulating the RAS/MAPK and PI3K/AKT/mTOR signaling pathways. Since 2022, numerous patents for SOS1 inhibitors have been published. The majority of SOS1 inhibitors are currently in the preclinical phase of development, with only a few progressing to clinical trials. However, these inhibitors face significant challenges in clinical studies, including limited efficacy of monotherapies, safety concerns, and the necessity to enhance PK properties. Despite their excellent in vitro performance, SOS1 inhibitors must address issues related to safety, pharmacokinetics, and pharmacodynamics in clinical applications.